PATHOLOGICAL-STUDY OF A RABBIT MODEL FOR SHIGELLOSIS

A nonsurgical rabbit model of enteric Shigella infection was developed for studying the pathogenesis and immunology of shigellosis and for e valuating Shigella vaccine candidates, In this model, rabbits are made susceptible to Shigella infection by a pre-inoculation conditioning p rocedure consisting of a 36-h nonfeeding period, with 250 mg of tetrac ycline administered in 250 mi of drinking water, 75 mg of cimetidine g iven intravenously, and two 15-ml doses of 5% sodium bicarbonate given orally immediately before orogastric administration of the bacterial inoculum, Lastly 2 ml of tincture of opium is administered intraperito neally, With a virulent strain, Shigella flexneri 2a, the clinical and pathologic characteristics of shigellosis in this rabbit model were s tudied, Twenty hours after oral inoculation of 10(10) bacteria, all si x experimental rabbits developed diarrhea and were lethargic or moribu nd, whereas the four control rabbits inoculated with sterile broth rem ained healthy, Histologic examination revealed severe, diffuse, necrot izing ileitis with hemorrhage in experimental rabbits, whereas no lesi ons were found in the controls, Although the major site of necrosis in this rabbit model was the ileum, as opposed to the colon in humans an d nonhuman primates, the histologic morphology of the lesion was the s ame in the various hosts. Because it is relatively inexpensive and con venient, this model should facilitate study of the pathophysiology and immunology of shigellosis, thereby speeding development of oral vacci nes, which can be tested in this animal model.